Could managing obesity help cancer patients?

Michelle Harvie PhD SRD Research Dietitian

The Nightingale and Prevent Breast Cancer Centre University Hospital of South Manchester NHS Foundation Trust

Food Matters Live Wednesday 23rd November

Questions

How many cancer patients are obese?

Will managing weight: Stop cancer coming back / progressing ?

Reduce risks of CVD / diabetes & does this matter for cancer patients ?

Prevent second cancers?

Make cancer patients feel better?

Don’t pts lose weight anyway because of the cancer

treatments?

What research is being done? - our B-AHEAD breast

cancer trials

Current guidelines on weight

• General advice for cancer patients to be a healthy weight • Not advised for metastatic patients • Focus after active chemotherapy / radiotherapy

ASCO 2015 NHS/ Macmillan Cancer Support 2013

Are these guidelines evidence based?

World Cancer Research Fund

Excess weight increases risk of 14

cancers

1 Post-menopausal breast

2 Endometrial

3 Ovarian

4 Advanced prostate

5 Colorectal

6 Kidney

7 Pancreatic

IARC Working Group. N Engl J Med. 2016 25;375(8):794-8

8 Liver

9 Gallbladder

10 Gastric cardia

11 Oesophageal adenocarcinoma

12 Thyroid

13 Meningioma

14 Multiple myeloma

How many cancer patients are obese?

Cancer % with BMI > 30 Kg/ m2

Localised disease

Endometrial 39 - 47

Renal 42

Breast 23- 27

Colorectal 17 - 37

Ovarian cancer 12- 15

Prostate 30 – 40

Metastatic

Colorectal 12

Breast 22-27

Renehan et al in press JCO

Questions

Will managing weight stop cancer coming back / progressing ?

Obesity & outcome:Meta-analyses

No. of studies

Cancer - mortality (obese vs. normal weight)

Breast cancer

Kwan et al. 2012 4 cohorts BMI > 40 : 40% increase

Cecchini et al. 2016

4 adjuvant RCTs: ER positive: 30% increase

Colorectal

Sinicrope et al. 2014

21 adjuvant RCTs 11% increase

Prostate

Cao & Ma 2011 12 (mixed study types)

20% increase per 5 kg/m2

Obesity & outcome:Meta-analyses

No. of studies

Cancer - mortality (obese versus normal weight)

Endometrial cancer

Arem & Irwin 2013 12 (mixed study types)

Equivocal evidence 4 studies showed association; 8 found

no association

Ovarian cancer

Bae et al. 2016 17 (mixed study types)

Equivocal evidence

Renal cancer

Bagheri 2016 8 (mixed study types)

Equivocal evidence 28% increase per 5 kg/m2

but increased overall mortality

Heavier patients have worse prognostic tumours at diagnosis

Normal

weight

Overweight Obese

Tumour size 20mm 24mm 26mm

Grade 3 59% 64% 64%

Node positive 49% 54% 55%

Triple negative 21% 23% 27%

Copson ER Ann Oncol. 2015 26(1):101-12

2596 premenopausal breast cancer patients

Chemotherapy dose-capping

Authors,

country

Cancer Normal

weight

Over-

weight

Obese

Griggs

2005, USA Breast

Pittsburgh

Cohort study

9% 11% 20%

Chambers

2012, UK Colorectal FOCUS2 trial

12% 21% 60%

Au-Yeung

2014,

Australia

Ovarian Australian Ovarian

Cancer Study

39% 39% 67%

Relapse rates high if < 85% chemo dose & = no treatment Bonadonna G N Engl J Med.1995;332(14):901-6

30%

50%

Breast cancer: CMF vs. no chemotherapy

One randomised trial of low fat diet, weight loss & outcome – WINS (n = 2437)

Weight change at 1 year -2.7 low fat vs + 0.7 control

5 year follow up 24% reduction in recurrence or new contralateral breast cancer

Chlebowski et al 2006 JNCI 98: 24

15 year follow up Overall mortality ER-ve : 36% reduction Triple –ve : 56% reduction

Chlebowski et al 2014 San Antonio Breast Conference

Ongoing RCTs of weight control in early BC patients

Trial Trial centre Intervention Population N Results expected

SUCCESS-C

Hauner Germany

24 months Diet and exercise 5-10% weight loss

Overweight. After adjuvant chemotherapy

3547 2016 ?

DIANA-5 Berrino Italy

WCRF recommendations 5 year FUP

Any weight. Within 5 years of diagnosis

1208 2016 ?

NCKMA32 Goodwin International

5 years Metformin 850mg bd

Any weight. After adjuvant chemotherapy

3582 2020

Breast Cancer Weight Loss Study (BWEL)

Ligebel USA & Canada

Weight loss (diet and exercise)

BMI ≥27 kg/m2 Within 12 months of diagnosis

3136 2030

We are hoping to set up a UK weight loss & outcome trial

Questions

Will managing weight reduce risks of CVD / diabetes & does this matter for cancer patients ?

Cardiovascular risk: Breast cancer patients

Cardiotoxicity • Anthracyclines • HER-2 inhibitors • Radiotherapy

Increase thrombotic events • Hormonal therapies eg. tamoxifen • Antiangiogenic drugs

Bardia A Breast Cancer Res Treat.2012;131(3):907-14.

N = 415 post menopausal early BC pts 10 year risk of BC recurrence & CVD event

BC> CVD 20%

BC=CVD 43%

CVD>BC 37%

Obesity increases non-cancer

deaths

Cancer Risk of non-cancer death Obese vs. normal weight patients

Kwan et al 2012

Breast n = 14,948

BMI 35-40 40% increase BMI >40 3 x risk

Campbell et al 2012

Colorectal n = 2303

Per 5kg / m2 28% increase

Questions

Will managing weight prevent second cancers?

Obesity increases second cancers

amongst cancer patients

Cancer patients

Type of secondary cancer

Druesne-Pecollo 2012

Breast 8 studies n= 27,230

Contralateral breast 37% increase Endometrial 96% increase Colorectal 89% increase

Gibson 2014 Colorectal 5 studies

n = 11,598

Any weight related cancer 47% increase Endometrial cancer 341% increase

Questions

Will managing weight make cancer patients feel better?

Weight loss programmes increase well-being in the short term

Outcome Baseline 6 M 12 M 24 M

Vitality ( SF36)

Intervention 60.5 (1.36) 65.1 (1.20) 62.2 (1.25) 60.5 (1.28)

Control 60.5 (1.37) 62.4 (1.23) 61.0 (1.29) 63.2 (1.31)

p value <0.05 NS NS

BC symptom score

Intervention 1.99 (0.03) 1.89 (0.03) 2.01 (0.03) 1.99 (0.03)

Control 2.02 (0.03) 2.02 (0.03) 2.07 (0.03) 2.02 (0.03)

p value <0.05 NS NS

Depression(CES-D)

Intervention 9.9 (0.50) 11.4 (0.44) 11.9 (0.45) 11.8 (0.47)

Control 9.7 (0.50) 10.6 (0.44) 10.9 (0.47) 9.9 (0.47)

p value NS NS <0.05

Mean (SEM)

692 early breast cancer patients – 12 month programme

Demark – Wahnefried Breast Cancer Res Treat. 2015; 154(2): 329–337

Questions

Don’t pts lose weight anyway because of the cancer treatments?

86 early BC patients 15- 17 weeks of chemotherapy

Need to prevent weight gain during adjuvant chemotherapy for BC patients

Dieli-Conwright Cancer 2016;122(17):2646-53

Conclusions How many cancer patients are obese?

Significant problem

Will managing weight:

• Stop cancer coming back / progressing ?

Possibly breast, colorectal , prostate

• Reduce risks of CVD / diabetes & does this matter for cancer patients ?

Yes Yes for some cancers i.e. breast cancer

• Prevent second cancers?

Yes

• Make cancer patients feel better?

Yes if we can keep weight off

• Don’t pts lose weight anyway because of the cancer treatments?

No, need to prevent weight gain for breast & possibly prostate & colorectal cancer

Patient feedback …

“Gives women some control.”

“Helps overall self-esteem if you don’t put

weight on.”

“I was glad I was on the diet and actually

managed to lose weight!”

“It has been a great help to me and given me

something to focus on apart from the chemo.”

Acknowledgements

Prevent Breast Cancer

Breast Cancer Research Trust

Anticancer Fund

Our Trial Participants

Funding Lifestyle Research Team

Co-investigators Sacha Howell Tony Howell Anne Armstrong Nigel Bundred Lee Graves Mark Mattson Judy Adams Louise Gorman

Mary Pegington Nina Brogden Claire Lindsay Kath Sellers Grace Cooper Debbie McMullen Pam Coates Lesley Coates Cheryl Barlow Prevent BC Volunteers PIs & research nurses in recruiting centres

Lead Research Dietitian Dr Michelle Harvie